Lamotrigine as an Add-on Treatment for Depersonalization Disorder: A Retrospective Study of 32 Cases Mauricio Sierra, MD, PhD, Dawn Baker, DClinPsy, Nicholas Medford, MRCP, MRCPsych, Emma Lawrence, PhD, Maxine Patel, MRCPsych, Mary L. Phillips, MD, and Anthony S. David, MD Abstract Objectives: Depersonalization disorder (DPD) is a chronic condition characterized by the persistent subjec- tive experience of unreality and detachment from the self. To date, there is no known treatment. Lamotrigine as sole agent was not found to be effective in a previous small double-blind, randomized crossover trial. However, evidence from open trials suggests that it may be beneficial as an add-on medication with antidepressants. Methods: We report here an extended series of 32 patients with DPD in whom lamotrigine was prescribed as an augmenting medication. Most of the patients were receiving selective serotonin reuptake inhibitors. Results: Fifty-six percent (n = 18) of patients had a more than or equal to 30% reduction on the Cambridge Depersonalization Scale score at follow-up. Both maximum dose of lamotrigine used and before treatment Cambridge Depersonalization Scale scores showed positive correlations with the percentage of response. Conclusions: The results of this trial suggest that a significant number of patients with DPD may respond to lamotrigine when combined with antidepressant medication. The results are sufficiently positive to prompt a larger controlled evaluation of lamotri- gine as ‘‘add-on’’ treatment in DPD. Key Words: depersonalization, derealization, dissociation, lamotrigine, depression, selective serotonin reuptake inhibitor, glutamate, CDS (Clin Neuropharmacol 2006;29:253Y258) D epersonalization disorder (DPD) is operationally defined as ‘‘an alteration in the perception or experience of the self’’ in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and is classified along with derealization under the heading Dissociative Disorders. 1 In the International Classification of Diseases, 10th Revision, the ‘‘depersonalization- derealization syndrome’’ is classed as a separate neurotic disorder. The 2 criteria are very similar: both note the same core symptoms, with intact ‘‘insight.’’ 2 Comorbid anxiety or depressive symptoms often accompany it, but to make a diagnosis of DPD, it must be clear that the condition does not occur exclusively in the presence of the comorbid condition. 1 The onset is in adoles- cence or early adult life. The condition may be episodic but is more often chronic and persistent and may be disabling. 3,4 Although the prevalence of DPD in the general population is unknown, an estimate of 1% has been suggested on the basis of community surveys. 5 Ross reported a preva- lence estimate of 2.4% of persistent deper- sonalization in a nonclinical population in Canada using a postal survey. 6 A large US phone survey indicated that 19% of 1008 adults had at least 1 episode of depersonal- ization in the previous 12 months. 7 As a comorbid condition, its prevalence seems much higher. Brauer et al 8 found that 80% of 212 psychiatric inpatients admitted to present or past depersonalization, whereas 12% reported severe and lasting experiences. Similarly, Noyes et al 9 found that 40% of 100 psychiatric inpatients endorsed at least 5 features of depersonalization. DOI: 10.1097/01.WNF.0000228368.17970.DA 253 Original Article CLINICAL NEUROPHARMACOLOGY Volume 29, Number 5 September - October 2006 Depersonalisation Research Unit, Psychological Medicine, Institute of Psychiatry, London, UK. Address correspondence and reprint requests to Mauricio Sierra, MD, PhD, Depersonalisation Research Unit, Psychological Medicine, Institute of Psychiatry, PO Box 68, Denmark Hill 103, London SE5 8AZ, UK; E-mail: M.Sierra-Siegert@iop.kcl.ac.uk Copyright Ó 2006 by Lippincott Williams & Wilkins Copyr ight © Lippincott Williams & Wilkins. Unauthor iz ed reproduction of this article is prohibited.